Original articles

Volume XLIV n. 2 - June 2025

Cancer and benign tumors in myotonic dystrophy, facioscapulohumeral muscular dystrophy, and oculopharyngeal muscular dystrophy: a 23-year, single-center, retrospective study

Authors

Naman Bareja , Brinda Desai , Michal Vytopil , Jayashri Srinivasan , Mehdi Ghasemi

Key words: oculopharyngeal muscular dystrophy (OPMD), Myotonic dystrophy, facioscapulohumeral muscular dystrophy (FSHD), cancer, melanoma, thyroid tumor
DOI: 10.36185/2532-1900-997
Publication Date: 2025-06-30

Abstract

Objectives. Some muscular dystrophies, such as myotonic dystrophy type 1 and 2 (DM1 and DM2), facioscapulohumeral muscular dystrophy (FSHD), and oculopharyngeal muscular dystrophy (OPMD), are caused by genetic mutations that may affect the expression and function of various cancer-related genes. We assessed the frequency and type of cancers and benign tumors in patients with DM1, DM2, FSHD, and OPMD.
Methods. We conducted a single-center, retrospective, cross-sectional study on patients with DM1, DM2, FSHD, and OPMD at our institution from January 2000 to September 2023.
Results. Seventy seven (46 female) DM1, 20 (15 female) DM2, 40 (18 female) FSHD, and 46 (22 female) OPMD patients were included, among which 22 (28.57%), 9 (45%), 7 (17.5%), and 15 (32.61%) patients had at least one cancer, respectively. Median age (range) of patients where presence or absence of cancer was ascertained was 65 (18-87), 63.5 (45-86), 61 (27-83), and 71.5 (40-82) years, respectively (P<0.0001). Overall, non-sex-related cancers were more frequent than sex-related cancers among all patients together. Independent to sex and age, DM1 patients had an increased risk of non-sex-related cancers compared to non-DM cases. Melanoma (P<0.01) and testicular (P<0.05) cancers were significantly more frequent in DM2 and OMPD patients, respectively. DM patients had also increased risk of non-sex related benign tumors (including skin and thyroid benign tumors) compared to non-DM patients.
Conclusions. Our study highlights the differences in the prevalence of cancers and benign tumors among patients with DM1, DM2, FSHD, and OPMD, underscoring the potential need for regular screening for specific cancers.

Introduction

Myotonic dystrophy (DM), facioscapulohumeral muscular dystrophy (FSHD), and oculopharyngeal muscular dystrophy (OPMD) are the most common adult-onset genetic muscular dystrophies, all characterized by progressive muscle weakness and wasting 1-4. DM is a complex autosomal-dominant disorder with multisystem involvement, marked by muscle weakness, myotonia, and systemic manifestations 5 6. There are two main subtypes: (i) DM1: Caused by a CTG repeat expansion in the DMPK (DM1 protein kinase) gene 7, and (ii) DM2: Associated with a CCTG repeat expansion in the CNBP (ZNF9) gene 8. With a prevalence of 1 in 8,000 individuals 1 9, DM presents a significant health concern, particularly due to its potential link to increased cancer risk 10 11. FSHD involves the progressive weakening of muscles, particularly in the face, shoulder blades, and upper arms. Approximately 95% of patients are diagnosed with autosomal dominant FSHD type 1 (FSHD1). The remaining 5% are classified as having FSHD type 2 (FSHD2), which is characterized by digenic inheritance. This form results from an additional genetic mutation that leads to the abnormal derepression of the double homeobox 4 (DUX4) gene 12. OPMD is marked by muscle weakness, primarily affecting the eyelids and throat, leading to ptosis and dysphagia. It results from an abnormal expansion of a polyalanine tract in the PABPN1 (poly[A] binding protein nuclear 1) gene 13.

Several studies have documented increased cancer risk in DM patients 11 14, with pilomatricomas being the most reported neoplasms 15. While much of the research has focused on DM1, evidence suggests an elevated cancer frequency in both DM1 and DM2 compared to the general population. The most reported tumors include pilomatricomas 15 with consensus-guidelines recommending cancer screening in adults with DM1 for this benign skin tumor 16. Other cancers linked to DM include thyroid 17, skin 18, thymomas 19 and sex-related cancers such as endometrial, uterine, and testicular cancers 17 20 21. Notably, Cancer is reported to be the third leading cause of death in individuals with DM, responsible for approximately 10-15% of mortalities 11. Proposed mechanisms include the upregulation of Wnt/β-catenin signaling, RNA-mediated defects in mismatch repair genes, dysregulation of miR-200 tumor suppressor genes, and impaired DNA repair machinery, which may explain the heightened cancer risk and offer potential therapeutic targets 11 22.

Despite growing research on the potential cancer risks in patients with DM and other muscular dystrophies, such as Duchenne muscular dystrophy 23 24, there is limited evidence exploring this association in conditions like FSHD and OPMD. Evaluating the cancer frequency and types in these patients, in comparison to those with DM, can enhance our understanding of these relationships and lead to better recommendations for cancer screening. Therefore, the aim of the present 23-year retrospective study is to assess the cancer frequency and types in patients with DM, FSHD, and OPMD. By analyzing long-term data from a single center, this study seeks to provide insights into cancer susceptibility in these conditions and inform future screening and management strategies.

Methods

In this retrospective, cross-sectional study, patients with diagnosis of DM1, DM2, FSHD, and OPMD were identified through billing codes using the SlicerDicer in Epic system (a cloud-based electronic health records [EHR] system utilized at Lahey Hospital). This tool was used to query for outpatients seen in the neurology clinics at Lahey Hospital Medical Center (Burlington, Massachusetts) between January 2000 and December 2023 with an International Classification of Diseases (ICD)-10 or ICD-9 codes for the following diagnoses: myotonic dystrophy type 1 (DM1), myotonic dystrophy type 2 (DM2), facioscapulohumeral muscular dystrophy (FSHD), and oculopharyngeal muscular dystrophy (OPMD). This tool automatically eliminates duplicates, yielding unique medical record numbers (MRNs) and patient names based on these diagnoses. The study was approved by the institutional review board (IRB number: 00000374, study number: 20233174).

Each medical record was reviewed to identify genetically confirmed DM1, DM2, FSHD and OPMD adult (≥ 18 years old) patients at the time of this study. The absence of a confirmatory genetic diagnosis, misdiagnosis (e.g., incorrect ICD-9 or ICD-10 coding), or missing clinical data in electronic records was considered an exclusion criterion. Medical charts were reviewed for patients with diagnosis of DM1 and DM2 to determine presence or absence of tumors, along with further categorization of tumors, including benign tumor or cancer, organ system involved and pathological diagnosis of tumor when present. Medical records for patients with OPMD and FSHD were reviewed for tumors using similar methods, to establish a non-DM cohort. Other variables that were collected for the study included gender, age of patients in clinic note where past medical history of presence or absence of cancer ascertained (years), and race (white or not).

Statistical analyses

Baseline demographic and clinical characteristics were presented, with continuous variables summarized as medians (ranges) and categorical variables as proportions. The Shapiro-Wilks test was utilized to assess normality within groups. For non-normally distributed groups, we applied the Wilcoxon rank sum test or the non-parametric Kruskal-Wallis test, incorporating Bonferroni correction for multiple comparisons. For normally distributed groups, we used either the two-sample t-test or analysis of variance (ANOVA). Logistic regression models to determine whether DM1 or DM2 diagnosis (relative to non-DM) are independently associated with cancer, non–sex-related cancer, sex-related cancer, benign tumor, non–sex-related benign tumor, and sex-related benign tumor a occurrence. P value less than 0.05 was considered statistically significant. All statistical analyses were performed using SAS® OnDemand for Academics software.

Results

Cancer Frequency

Figure 1 depicts the sequential steps undertaken to finalize the patient numbers for each group in the study, which ultimately comprised 183 individuals diagnosed with adult-onset muscular dystrophies (DM1, DM2, FSHD, and OPMD). Among these, 97 patients were diagnosed with DM, comprising 77 individuals (46 females, median age 65 years) with DM1 and 20 individuals (15 females, median age 63.5 years) with DM2. In the non-DM group, 46 patients (22 females, median age 71.5 years) were diagnosed with OPMD, and 40 patients (18 females, median age 61 years) were diagnosed with FSHD (Tab. I).

The univariate analysis revealed no statistically significant differences in the prevalence of cancers among the DM1 (28.6%, 22 patients), DM2 (45%, 9 patients), FSHD (17.5%, 7 patients), and OPMD (32.61%, 15 patients) groups (P = 0.142). This finding extended to both sex-related (P = 0.7913) and non-sex-related (P = 0.2801) cancers (Tab. I). The groups displayed notable demographic differences. DM1 patients were significantly older than those with DM2 (P = 0.0019) but younger than the non-DM patients (P < 0.0001). Furthermore, FSHD patients were generally older than individuals in other groups. Although there were no significant sex differences between the DM1 and DM2 groups, the DM2 group exhibited a male predominance compared to the non-DM group (P < 0.05).

To eliminate the possibility that our cancer frequency findings were influenced by age and sex differences, we performed logistic regression analyses (Table 2). These models considered cancer occurrence (overall, sex-related, and non-sex-related) as the outcome variable, with the diagnosis (DM1, DM2, or non-DM as the reference) as the independent variable, adjusting for age and sex. Our analysis revealed a significant association between a DM1 diagnosis and the presence of cancer, compared to a non-DM diagnosis (odds ratio [OR] 2.718, 95% confidence interval [CI] 1.159-6.373, P < 0.05), independent of age and sex (Tab. II). Conversely, no significant association was found for DM2 (OR 2.506, 95%CI 0.827-7.598, P = 0.1044). Additionally, after adjusting for age and sex, we noted an increased risk of non-sex-related cancers in DM1 patients relative to non-DM patients (OR 3.013, 95%CI 1.198-7.577, P < 0.05) but no significant differences in the risk of sex-related cancers for either DM1 or DM2 compared to non-DM (Tab. II). As anticipated, older age was independently associated with a higher occurrence of cancer, whereas sex was not a significant factor (Tab. II).

Benign Tumor Frequency

The univariate analysis revealed significant (P < 0.0001) differences in the prevalence of benign tumors among the groups: DM1 (44.16%, 34 patients), DM2 (55%, 11 patients), FSHD (25%, 10 patients), and OPMD (10.87%, 5 patients). This finding was significant for non-sex-related benign tumors (P = 0.0008) but not for sex-related benign tumors (P = 0.4746) (Tab. I). We further examined the frequency of skin and thyroid benign tumors among all patients. The results indicated a higher overall frequency of these benign tumors in DM1 patients compared to non-DM patients (Tab. I). However, there was no significant difference in the frequency of these tumors between DM1 and DM2 groups. Notably, neither FSHD nor OPMD patients exhibited thyroid benign tumors. Skin benign tumors were also not observed in FSHD patients.

To ensure the differences in benign tumors were not driven by variations in age and sex, we conducted logistic regression analyses (Tab. II). Our results showed a significant association between a diagnosis of either DM1 (OR 5.737, 95% CI 2.424-13.579, P < 0.0001) or DM2 (OR 5.034, 95% CI 1.692-14.981, P = 0.0037) and the presence of benign tumors, compared to non-DM diagnoses, independent of age and sex (Table 2). Furthermore, after adjusting for age and sex, we observed an increased risk of non-sex-related benign tumors in DM1 (OR 5.316, 95% CI 2.148-13.154, P = 0.0003) and DM2 (OR 4.968, 95% CI 1.621-15.228, P = 0.005) patients compared to non-DM patients. However, there were no significant differences in the risk of sex-related benign tumors between DM1 or DM2 and non-DM patients (Tab. II). Additionally, older age and male sex were independently associated with a higher occurrence of benign tumors (Tab. II).

Frequency of Organ-Specific Cancers

Sex-related cancers showed that breast and testicular cancers were more prevalent in DM1 and OPMD patients, respectively, compared to other groups (Tab. III). However, the univariate analysis revealed no statistically significant differences in the frequency of sex-related cancers (breast, ovary, endometrium, and prostate cancers) across groups, except for testicular cancer, which was only present in OPMD patients (P = 0.0131). Additionally, ovarian cancer was not reported in any patients within our cohort. Among non-sex-related cancers, melanoma was observed in 3 patients with DM2 (15%) and not in other groups of DM1, FSHD, and OPMD cases (P = 0.0011). As shown in Table III, no significant differences were found in occurrence of other non-sex-related cancers among the groups.

Discussion

Our retrospective cross-sectional study demonstrated an increased risk of cancers in DM1 patients and benign tumors in both DM1 and DM2 patients compared to non-DM groups (comprising patients with FSHD and OPMD), independent of sex and age. Additionally, we observed a higher risk of non-sex-related cancers in DM1 patients compared to non-DM patients, but this was not observed in DM2 patients. Moreover, melanoma was exclusively reported in DM2 patients (15%), and testicular cancer was only present in OPMD patients (8.7%). The prevalence of both skin and thyroid benign tumors was higher in both DM1 and DM2 groups compared to non-DM patients, and higher in DM1 cases compared to DM2 groups.

Our data aligns with previous findings 11 17 18 20, suggesting that there is increased risk of cancers in DM1 and argues against the notion that the increased cancer risk is a nonspecific, indirect consequence of having a muscular dystrophy diagnosis. We did not find an overall increased cancer risk in DM2 patients compared to non-DM patients, which contrasts with findings from a recent study 11. This discrepancy could be attributed to the smaller sample size in our study, limiting the statistical power to detect cancer risk. There is also evidence suggesting that the risk of skin cancers, including melanoma, is higher in DM patients 11 18 25. We observed that melanoma was significantly more prevalent in DM2 cases and was not reported in DM1, OPMD, and FSHD cases. This indicates that, although the overall cancer risk is higher in DM patients, the types of cancer may differ between DM1 and DM2 cases. Previous studies with DM1-predominant cohorts have reported an increased risk of ovarian and endometrial cancers, as well as non-sex-related cancers of thyroid, pancreatic, colon, and brain cancers 14 22 26. However, our study did not observe these associations.

Notably, testicular cancers were only observed in OPMD patients and were absent in DM1, DM2, and FSHD cases within our cohort. Overall, there is not a significant body of evidence specifically linking OPMD to an increased prevalence of cancer. OPMD is caused by an abnormal expansion of a polyalanine tract in the PABPN1 gene 13. Notably, the polyalanine expansion mutation is thought to confer a toxic gain-of-function on mutant PABPN1, leading to the formation of aggregates within skeletal myocyte nuclei 27. This gene plays a pivotal role in RNA processing and stability 28, as well as in regulating cell growth and differentiation 29, processes that are integral to cancer development. Recent studies have demonstrated that PABPN1 is overexpressed in many human prostate cancers and is associated with poor prognosis, invasion, and metastasis 30 31. Additionally, PABPN1 promotes cell proliferation, migration, and invasion in clear cell renal cell carcinoma 32. PABPN1 expression was significantly higher in patients with colorectal cancer tissues compared to normal individuals, and its elevated levels were associated with a poorer prognosis for colorectal cancer 33. Some case reports and small studies have suggested a potential link between the PABPN1 gene and bladder cancer 34. Two of our OPMD cases were also diagnosed with renal/bladder cancers, but there were no such reports of these cancers in DM1 or FSHD cases within our cohort. However, there is currently no well-established link between the PABPN1 gene and testicular cancer. Additionally, it remains unclear whether PABPN1 is overexpressed in OPMD, which would support a proposed connection with the reported cancer cases. Further research is necessary to investigate this potential association.

Our study was also notable for significantly higher occurrence of benign tumors, especially non-sex-related ones including skin and thyroid benign tumors, in DM patients compared to non-DM patients. This finding is consistent with the previous study 11, in which colon polyps, thyroid nodules, and skin benign tumors were the most frequent benign tumors observed in DM1 and DM2 patients compared with OPMD and FSHD patients.

The genetic mechanisms and underlying pathophysiology responsible for tumorigenesis in patients with DM remain poorly understood. DM1 is caused by the expansion of a CTG trinucleotide repeat in the 3’ untranslated region (UTR) of the DMPK gene. DM2 results from the expansion of a CCTG tetranucleotide repeat in intron 1 of the CNBP gene. Both expansions occur in the noncoding regions of these genes, which suggests that altered RNA splicing and metabolism might play a crucial role in the disease process. The accumulation of toxic RNA within the nucleus is a hallmark of DM. This toxic RNA interacts with RNA-binding proteins, such as CUG-BP1 and muscle blind-like (MBNL) proteins, leading to their sequestration and functional disruption. These RNA-binding proteins are essential for normal RNA splicing, and their dysfunction results in widespread splicing abnormalities, affecting numerous downstream gene functions. Mueller et al. 35 proposed that DM predisposes patients to neoplasms through the upregulation of β-catenin, a key component of the Wnt signaling pathway. The Wnt/β-catenin signaling pathway is crucial for cell proliferation, differentiation, and survival. Dysregulation of this pathway can lead to uncontrolled cell growth and cancer 36. In addition to β-catenin upregulation, disruptions in RNA splicing factors, caused by the sequestration of proteins like CUG-BP1 and MBNL, can affect multiple downstream genes involved in cell cycle regulation, apoptosis, and other critical cellular processes 37.

Although these hypotheses are promising and provide valuable insights into the potential mechanisms linking DM to cancer, further research is needed to fully understand the relationship between RNA disruption, Wnt signaling, and tumor formation in DM patients. Detailed studies investigating the molecular pathways involved and the identification of specific genes affected by these disruptions will be crucial for developing targeted therapies and improving patient outcomes.

FSHD is primarily associated with the aberrant expression of the DUX4 gene in skeletal muscle tissue 3. In recent years, several studies have established connections between DUX4 expression and oncological conditions 38. For instance, a 2019 study identified alterations in blood tumor samples 39, a finding subsequently corroborated by additional research suggesting that DUX4 mutations may serve as a biomarker for acute lymphoblastic leukemia 40-42. Furthermore, the involvement of DUX4 alterations has been observed in round-cell sarcomas, including Ewing-like sarcomas 43. Notably, in an aggressive subtype of sarcoma predominantly affecting pediatric and young patients, the pathological event is driven by a fusion between the Capicua protein (CIC) and DUX4. While CIC typically functions as a transcriptional repressor under non-pathological conditions, its fusion with DUX4 transforms it into a transcriptional activator 44-46. The resulting CIC-DUX4 fusion drives the development of small round-cell sarcomas that are distinct from Ewing sarcoma. This fusion has been recognized as an oncogenic mechanism, though altered DUX4 has also demonstrated tumor suppressor functions in cancers such as synovial sarcoma and colon cancer 47 48. Additionally, RNAs encoding DUX4 and its target genes have been detected across a broad spectrum of cancers 49. Recent investigation indicates that DUX4 expression in malignancies can transiently activate an early embryonic program, characterized by trophectoderm-specific genes and epithelial-to-mesenchymal transition processes, potentially contributing to cancer progression or metastasis 50. In our cohort, only 7 FSHD patients (17.5%) were diagnosed with cancer - a lower prevalence compared to other muscular dystrophies included in the study. Clinical data on the frequency of cancer in FSHD patients remains limited. A recent study on 31 FSHD1 patients and 30 non-affected (non-FSHD1) family members of these patients reported that gastrointestinal cancers, including gastric and colorectal cancers, were significantly more prevalent in FSHD1 patients (32.3%) compared to non-affected individuals (6.7%), particularly in those over the age of 40. Notably, this increased prevalence was not associated with the D4Z4 repeat number 51. Conversely, the incidence of cancers in non-gastrointestinal tissues was found to be comparable between FSHD1 patients and non-affected individuals 51. These findings underscore the need for additional studies with larger sample sizes to further investigate this association.

Conclusions

Based on the findings from our cohort and prior studies, we advocate for regular cancer or benign tumor screening in DM patients, with a particular emphasis on non-sex-related cancers such as those affecting the thyroid and skin. An annual thyroid gland palpation is recommended for patients with DM. In cases where abnormalities are identified, further evaluation through thyroid ultrasound and thyroid function blood tests should be considered. The 2018 consensus-based care guidelines for adults with DM1 provide specific recommendations for tumor detection 16. These include: (i) identifying pilomatricomas, which are benign calcifying skin tumors derived from hair matrix cells, and referring patients to surgeons for safe removal; (ii) educating patients on how to detect pilomatricomas themselves; (iii) adhering to standard cancer screening protocols recommended for the general population, with a focus on breast, testicular, cervical, and colon cancers; and (iv) assessing new symptoms in the central nervous system, abdominopelvic region, and thyroid for potential malignancies. For DM2, similar recommendations were issued in 2019, with the exception of pilomatricoma detection, as these are uniquely associated with DM1 52. Additionally, further research is essential to gain a deeper understanding of the cancer risks associated with DM and to develop targeted screening and prevention strategies for this patient population.

The main limitations of this study include its relatively small sample size and retrospective design, which limit the generalizability of the findings and reduce the ability to detect subtle cancer risks. Personal and environmental factors, such as smoking and comorbidities, which are significant contributors to tumorigenesis, were not assessed in this research and represent an additional limitation. Moreover, a comparative analysis with the general population of the same age range would provide more meaningful insights into the prevalence of cancer and benign tumors in muscular dystrophies like FSHD and OPMD. This study, however, focused exclusively on analyzing four muscular dystrophies and comparing these groups with one another.

Future investigations should prioritize larger, prospective studies to better delineate the cancer risk profiles of various muscular dystrophies relative to the general population. Such studies are also necessary to confirm cancer risk, define the cancer spectrum in FSHD and OPMD, and explore the molecular mechanisms contributing to the increased tumor risks observed in DM1, DM2, OPMD, and FSHD. These efforts are critical before revising cancer screening recommendations, particularly for FSHD and OPMD patients, compared to the general population.

Conflict of Interest Statement

None of the authors has any conflict of interest to disclose.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Authors’ contribution

NB: literature review and execution of research project; review and critique of the manuscript; preparing the first draft of paper’s tables. BD: execution of research project; review and critique of the final manuscript. MV and JS: conception; revising of the first draft of manuscript; review and critique of the final manuscript. MG: conception, organization, literature review, and execution of research project; data analysis; revising of the first draft of manuscript; review and critique of the final manuscript.

Ethical consideration

We confirm that we have read the Journal’s position on issues involved in ethical publication and affirm that this report is consistent with those guidelines. The use of human subjects as well as all study procedures for this clinical study were approved by the institutional review board at Lahey Hospital and Medical Center (IRB number: 00000374, study number: 20233174).

History

Received: January 23, 2025

Accepted: March 17, 2025

Figures and tables

Figure 1. Schematic overview of the steps taken to determine the final patient numbers for each group included in the study, encompassing diagnoses of myotonic dystrophy types 1 and 2 (DM1 and DM2), facioscapulohumeral muscular dystrophy (FSHD), and oculopharyngeal muscular dystrophy (OPMD).

Variables DM1 (n = 77) DM2 (n = 20) FSHD (n = 40) OPMD (n = 46) Non-DM (n = 86) DM1 vs DM2 P DM1 vs non-DM P DM2 vs Non-DM P All groups P
Demographics
Age (years), median (range) 65 (18-87) 63.5 (45-86) 61 (27-83) 71.5 (40-82) 67 (27-83) 0.0019 < 0.0001 0.8147 < 0.0001
Sex, female (%) 46 (59.74) 15 (75.00) 18 (45.00) 22 (47.83) 40 (46.51) 0.2996 0.1161 0.0262 0.0914
Race, white (%) 76 (98.70) 18 (90.00) 39 (97.50) 46 (100.00) 85 (98.84) 0.1070 1.0000 0.0906 0.0716
Cancer, n (%)
Any Cancer 22 (28.57) 9 (45.00) 7 (17.50) 15 (32.61) 22 (25.58) 0.1844 0.7253 0.1045 0.1420
Sex-related cancer 5 (6.49) 2 (10.00) 3 (7.50) 5 (10.87) 9 (10.47) 0.6309 0.4136 1.0000 0.7913
Non-sex-related cancers 17 (22.08) 7 (35.00) 4 (10.00) 9 (19.57) 14 (16.28) 0.2532 0.4249 0.0690 0.2801
Non-melanoma skin cancer 14 (18.18) 3 (15.00) 1 (2.50) 7 (15.22) 8 (9.30) 1.0000 0.1122 0.4310 0.0810
Melanoma 0 (0) 3 (15.00) 0 (0) 0 (0) 0 (0) 0.0077 - 0.0059 0.0011
Thyroid cancer 2 (2.60) 0 (0) 1 (2.50) 1 (2.17) 2 (2.33) 1.0000 1.0000 1.0000 1.0000
Benign Tumors, n (%)
Any benign tumors 34 (44.16) 11 (55.00) 10 (25.00) 5 (10.87) 15 (17.44) 0.4548 0.0003 0.0011 < 0.0001
Sex-related benign tumor 10 (12.99) 2 (10.00) 7 (17.50) 3 (6.52) 10 (11.63) 1.0000 0.8154 1.0000 0.4746
Non-sex-related benign tumor 27 (35.06) 9 (45.00) 7 (17.50) 4 (8.70) 11 (12.79) 0.4441 0.0009 0.0025 0.0008
Skin benign tumor 9 (11.69) 2 (10.00) 0 (0) 1 (2.17) 1 (1.16) 1.0000 0.0067 0.0906 0.0328
Thyroid benign tumor 9 (11.69) 4 (20.00) 0 (0) 0 (0) 0 (0) 0.4593 0.0009 0.0010 0.0011
Table I. Demographics and frequency of cancers and benign tumors (univariate analyses) in patients with myotonic dystrophy type 1 and 2 (DM1 and DM2), facioscapulohumeral muscular dystrophy (FSHD), and oculopharyngeal muscular dystrophy (OPMD) patients. Non-DM patients include those with FSHD and OPMD.
Variables Odds Ratio 95% Confidence Interval P value
Outcome: Cancer
Age 1.070 1.037-1.103 < 0.0001
Sex 0.657 0.321-1.345 0.2501
DM1 Diagnosis 2.718 1.159-6.373 0.0214
DM2 Diagnosis 2.506 0.827-7.598 0.1044
Outcome: Non-sex-Related Cancer
Age 1.057 1.024-1.091 0.0006
Sex 0.913 0.419-1.987 0.8181
DM1 Diagnosis 3.013 1.198-7.577 0.0191
DM2 Diagnosis 2.948 0.928-9.371 0.0669
Outcome: Sex-related Cancer
Age 1.062 1.013-1.114 0.0128
Sex 0.361 0.107-1.216 0.1000
DM1 Diagnosis 1.004 0.282-3.581 0.9947
DM2 Diagnosis 0.737 0.137-3.979 0.7229
Outcome: Benign Tumor
Age 1.034 1.007-1.062 0.0133
Sex 0.322 0.156-0.666 0.0022
DM1 Diagnosis 5.737 2.424-13.579 < 0.0001
DM2 Diagnosis 5.034 1.692-14.981 0.0037
Outcome: Non-sex-Related Benign Tumor
Age 1.031 1.003-1.059 0.0276
Sex 0.452 0.211-0.967 0.0408
DM1 Diagnosis 5.316 2.148-13.154 0.0003
DM2 Diagnosis 4.968 1.621-15.228 0.0050
Outcome: Sex-Related Benign Tumor
Age 1.014 0.980-1.048 0.4289
Sex 0.676 0.264-1.730 0.4139
DM1 Diagnosis 1.290 0.453-3.671 0.6335
DM2 Diagnosis 0.764 0.150-3.875 0.7448
Table II. Logistic regression models adjusted by age and sex. DM, myotonic dystrophy.
Variables DM1 (n = 77) DM2 (n = 20) FSHD (n = 40) OPMD (n = 46) Non-DM (n = 86) DM1 vs DM2 P DM1 vs non-DM P DM2 vs Non-DM P All groups P
Sex-Related Cancers, n (%)
Breast 4 (5.19) 2 (10.00) 1 (2.50) 1 (2.17) 2 (0.4734) 0.6001 0.4228 0.1605 0.4734
Ovary 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) - - - -
Endometrium 1 (1.30) 0 (0) 1 (2.50) 1 (2.17) 2 (2.35) 1.0000 1.0000 1.0000 1.0000
Prostate 0 (0) 0 (0) 1 (2.50) 0 (0) 1 (1.16) - 1.0000 1.0000 0.3279
Testes 0 (0) 0 (0) 0 (0) 4 (8.70) 4 (4.65) - 0.1227 1.0000 0.0131
Non-sex-Related Cancers, n (%)
Brain, 0 (0) 0 (0) 0 (0) 1 (2.17) 1 (1.16) - 1.0000 1.0000 0.5792
Head/neck 1 (1.30) 0 (0) 0 (0) 0 (0) 0 (0) 1.0000 0.4724 - 1.0000
Lung 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) - - - -
Gastrointestinal 0 (0) 1 (5.00) 2 (5.00) 0 (0) 2 (2.33) 0.2062 0.4984 0.4695 0.0724
Renal/Bladder 0 (0) 1 (5.00) 0 (0) 2 (4.35) 2 (2.33) 0.2062 0.4984 0.4695 0.0930
Carcinoid 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) - - - -
Hematologic 0 (0) 0 (0) 0 (0) 2 (4.35) 2 (2.33) - 0.4984 1.0000 0.2237
Liposarcoma 0 (0) 0 (0) 0 (0) 0 (0) 0 (0) - - - -
Table III. Frequency of sex- and non-sex-related cancers (univariate analyses) in patients with myotonic dystrophy type 1 and 2 (DM1 and DM2), facioscapulohumeral muscular dystrophy (FSHD), and oculopharyngeal muscular dystrophy (OPMD) patients. Non-DM patients include those with FSHD and OPMD.

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Naman Bareja - Department of Neurology, Tufts Medical Center, Boston, MA, USA

Brinda Desai - Department of Neurology, Lahey Hospital and Medical Center, Burlington, MA, USA

Michal Vytopil - Department of Neurology, Lahey Hospital and Medical Center, Burlington, MA, USA

Jayashri Srinivasan - Department of Neurology, Lahey Hospital and Medical Center, Burlington, MA, USA

Mehdi Ghasemi - Department of Neurology, Lahey Hospital and Medical Center, Burlington, MA, USA

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Bareja, N., Desai, B., Vytopil, M., Srinivasan, J., & Ghasemi, M. (2025). Cancer and benign tumors in myotonic dystrophy, facioscapulohumeral muscular dystrophy, and oculopharyngeal muscular dystrophy: a 23-year, single-center, retrospective study. Acta Myologica, 44(2). https://doi.org/10.36185/2532-1900-997
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